TRADD_MOUSE
ID TRADD_MOUSE Reviewed; 310 AA.
AC Q3U0V2;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Tumor necrosis factor receptor type 1-associated DEATH domain protein {ECO:0000305};
DE Short=TNFR1-associated DEATH domain protein {ECO:0000303|PubMed:16702408};
DE AltName: Full=TNFRSF1A-associated via death domain {ECO:0000303|PubMed:16702408};
GN Name=Tradd {ECO:0000303|PubMed:16702408, ECO:0000312|MGI:MGI:109200};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1] {ECO:0000312|EMBL:BAE33749.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NOD {ECO:0000312|EMBL:BAE33749.1};
RC TISSUE=Spleen {ECO:0000312|EMBL:BAE33749.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2] {ECO:0000312|EMBL:AAI32608.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain {ECO:0000312|EMBL:AAI32608.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION IN COMPLEX I WITH CHUCK; IKBKB AND IKBKG, AND INTERACTION
RP WITH TRPC4AP.
RX PubMed=14585990; DOI=10.1128/mcb.23.22.8334-8344.2003;
RA Soond S.M., Terry J.L., Colbert J.D., Riches D.W.H.;
RT "TRUSS, a novel tumor necrosis factor receptor 1 scaffolding protein that
RT mediates activation of the transcription factor NF-kappaB.";
RL Mol. Cell. Biol. 23:8334-8344(2003).
RN [4]
RP INTERACTION WITH KRT14; KRT16 AND KRT17, AND SUBCELLULAR LOCATION.
RX PubMed=16702408; DOI=10.1101/gad.1387406;
RA Tong X., Coulombe P.A.;
RT "Keratin 17 modulates hair follicle cycling in a TNFalpha-dependent
RT fashion.";
RL Genes Dev. 20:1353-1364(2006).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, INTERACTION WITH
RP TRIP12, AND MUTAGENESIS OF 297-GLU--LEU-299.
RX PubMed=22561347; DOI=10.1038/ncb2496;
RA Chio I.I., Sasaki M., Ghazarian D., Moreno J., Done S., Ueda T., Inoue S.,
RA Chang Y.L., Chen N.J., Mak T.W.;
RT "TRADD contributes to tumour suppression by regulating ULF-dependent p19Arf
RT ubiquitylation.";
RL Nat. Cell Biol. 14:625-633(2012).
RN [7]
RP INTERACTION WITH FADD.
RX PubMed=30185824; DOI=10.1038/s41418-018-0166-8;
RA Anderton H., Bandala-Sanchez E., Simpson D.S., Rickard J.A., Ng A.P.,
RA Di Rago L., Hall C., Vince J.E., Silke J., Liccardi G., Feltham R.;
RT "RIPK1 prevents TRADD-driven, but TNFR1 independent, apoptosis during
RT development.";
RL Cell Death Differ. 26:877-889(2019).
RN [8]
RP GLYCOSYLATION AT ARG-243 (MICROBIAL INFECTION).
RX PubMed=30902834; DOI=10.1074/mcp.ra118.001093;
RA Newson J.P.M., Scott N.E., Yeuk Wah Chung I., Wong Fok Lung T., Giogha C.,
RA Gan J., Wang N., Strugnell R.A., Brown N.F., Cygler M., Pearson J.S.,
RA Hartland E.L.;
RT "Salmonella effectors SseK1 and SseK3 target death domain proteins in the
RT TNF and TRAIL signaling pathways.";
RL Mol. Cell. Proteomics 18:1138-1156(2019).
CC -!- FUNCTION: Adapter molecule for TNFRSF1A/TNFR1 that specifically
CC associates with the cytoplasmic domain of activated TNFRSF1A/TNFR1
CC mediating its interaction with FADD (By similarity). Overexpression of
CC TRADD leads to two major TNF-induced responses, apoptosis and
CC activation of NF-kappa-B (By similarity). The nuclear form acts as a
CC tumor suppressor by preventing ubiquitination and degradation of
CC isoform p19ARF/ARF of CDKN2A by TRIP12: acts by interacting with
CC TRIP12, leading to disrupt interaction between TRIP12 and isoform
CC p19ARF/ARF of CDKN2A (PubMed:22561347). {ECO:0000250|UniProtKB:Q15628,
CC ECO:0000269|PubMed:22561347}.
CC -!- SUBUNIT: Stimulation of TNF-alpha receptor TNFRSF1A leads to the
CC formation of two distinct signaling complexes (PubMed:14585990). Plasma
CC membrane-bound complex I is composed of TNFRSF1A, TRADD, RIPK1, TRAF2
CC and BIRC2/c-IAP1 or BIRC3 which interacts with CHUCK/IKK-alpha,
CC IKBKB/IKK-beta and IKBKG/IKK-gamma promoting cell survival
CC (PubMed:14585990). Subsequently, TRADD, RIPK1 and TRAF2 dissociate from
CC TNFRSF1A and form cytoplasmic complex II with FADD and caspase CASP8
CC promoting cell apoptosis (By similarity). Within complex I, interacts
CC with TNFRSF1A/TNFR1, TRAF2 and kinase RIPK1 (By similarity). Within
CC complex I, interacts with TRPC4AP; the interaction promotes NF-kappa B
CC activation (PubMed:14585990). UXT1 associates with complex I; the
CC interaction prevents the formation of complex II (By similarity).
CC Within complex I Interacts with scaffold protein DAB2IP (By
CC similarity). Interacts with autophagy receptor SQSTM1 (By similarity).
CC Interacts with E3 ligase TRIP12 (PubMed:22561347). Interacts with
CC kinase HIPK2 (By similarity). Interacts with keratin KRT14
CC (PubMed:16702408). Interacts with keratin KRT18 (By similarity).
CC Interacts with KRT16 and KRT17 (PubMed:16702408). Interacts with FADD
CC (PubMed:30185824). Interacts with TOMM70 (By similarity).
CC {ECO:0000250|UniProtKB:Q15628, ECO:0000269|PubMed:14585990,
CC ECO:0000269|PubMed:16702408, ECO:0000269|PubMed:22561347,
CC ECO:0000269|PubMed:30185824}.
CC -!- INTERACTION:
CC Q3U0V2; Q60855: Ripk1; NbExp=2; IntAct=EBI-1544032, EBI-529119;
CC Q3U0V2; Q9QUK6: Tlr4; NbExp=3; IntAct=EBI-1544032, EBI-1534575;
CC Q3U0V2; P01375: TNF; Xeno; NbExp=2; IntAct=EBI-1544032, EBI-359977;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22561347}. Cytoplasm
CC {ECO:0000269|PubMed:22561347}. Cytoplasm, cytoskeleton. Note=Shuttles
CC between the cytoplasm and the nucleus. {ECO:0000269|PubMed:22561347}.
CC -!- DOMAIN: Requires the intact death domain to associate with
CC TNFRSF1A/TNFR1. {ECO:0000250|UniProtKB:Q15628}.
CC -!- PTM: (Microbial infection) Glycosylated at Arg-243 by S.typhimurium
CC protein Ssek1: arginine GlcNAcylation prevents homotypic/heterotypic
CC death domain interactions and assembly of the oligomeric TNFRSF1A/TNFR1
CC complex, thereby disrupting TNF signaling.
CC {ECO:0000269|PubMed:30902834}.
CC -!- DISRUPTION PHENOTYPE: Mice develop tumors. In a C57BL/6 genetic
CC background, mice exhibit a shorter lifespan than wild-type, but exhibit
CC low incidences of observable tumor formation. In the FVB/N background,
CC which is more tumor-prone, mice show a significant increas in the
CC spontaneous development of a broad range of tumor types.
CC {ECO:0000269|PubMed:22561347}.
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DR EMBL; AK156540; BAE33749.1; -; mRNA.
DR EMBL; BC132607; AAI32608.1; -; mRNA.
DR CCDS; CCDS22594.1; -.
DR RefSeq; NP_001028333.1; NM_001033161.2.
DR AlphaFoldDB; Q3U0V2; -.
DR SMR; Q3U0V2; -.
DR BioGRID; 214812; 7.
DR DIP; DIP-38039N; -.
DR IntAct; Q3U0V2; 9.
DR STRING; 10090.ENSMUSP00000034359; -.
DR iPTMnet; Q3U0V2; -.
DR PhosphoSitePlus; Q3U0V2; -.
DR EPD; Q3U0V2; -.
DR MaxQB; Q3U0V2; -.
DR PaxDb; Q3U0V2; -.
DR PRIDE; Q3U0V2; -.
DR ProteomicsDB; 260734; -.
DR Antibodypedia; 3894; 535 antibodies from 43 providers.
DR DNASU; 71609; -.
DR Ensembl; ENSMUST00000034359; ENSMUSP00000034359; ENSMUSG00000031887.
DR GeneID; 71609; -.
DR KEGG; mmu:71609; -.
DR UCSC; uc009nby.1; mouse.
DR CTD; 8717; -.
DR MGI; MGI:109200; Tradd.
DR VEuPathDB; HostDB:ENSMUSG00000031887; -.
DR eggNOG; ENOG502RXWE; Eukaryota.
DR GeneTree; ENSGT00390000002016; -.
DR HOGENOM; CLU_052183_0_0_1; -.
DR InParanoid; Q3U0V2; -.
DR OMA; QPCSRFL; -.
DR OrthoDB; 1024816at2759; -.
DR PhylomeDB; Q3U0V2; -.
DR TreeFam; TF331882; -.
DR Reactome; R-MMU-3371378; Regulation by c-FLIP.
DR Reactome; R-MMU-5218900; CASP8 activity is inhibited.
DR Reactome; R-MMU-5357786; TNFR1-induced proapoptotic signaling.
DR Reactome; R-MMU-5357905; Regulation of TNFR1 signaling.
DR Reactome; R-MMU-5357956; TNFR1-induced NFkappaB signaling pathway.
DR Reactome; R-MMU-5675482; Regulation of necroptotic cell death.
DR Reactome; R-MMU-69416; Dimerization of procaspase-8.
DR Reactome; R-MMU-75893; TNF signaling.
DR BioGRID-ORCS; 71609; 9 hits in 74 CRISPR screens.
DR PRO; PR:Q3U0V2; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q3U0V2; protein.
DR Bgee; ENSMUSG00000031887; Expressed in intestinal villus and 243 other tissues.
DR ExpressionAtlas; Q3U0V2; baseline and differential.
DR Genevisible; Q3U0V2; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
DR GO; GO:0002947; C:tumor necrosis factor receptor superfamily complex; ISO:MGI.
DR GO; GO:0070513; F:death domain binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0019900; F:kinase binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0005068; F:transmembrane receptor protein tyrosine kinase adaptor activity; ISO:MGI.
DR GO; GO:0005164; F:tumor necrosis factor receptor binding; ISO:MGI.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; ISO:MGI.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IGI:MGI.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR GO; GO:0051798; P:positive regulation of hair follicle development; IMP:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISO:MGI.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISO:MGI.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 3.30.70.680; -; 1.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR000488; Death_domain.
DR InterPro; IPR035712; TRADD.
DR InterPro; IPR009095; TRADD_N.
DR InterPro; IPR036729; TRADD_N_sf.
DR PANTHER; PTHR14913; PTHR14913; 1.
DR Pfam; PF00531; Death; 1.
DR Pfam; PF09034; TRADD_N; 1.
DR SMART; SM00005; DEATH; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF55044; SSF55044; 1.
DR PROSITE; PS50017; DEATH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Cytoplasm; Cytoskeleton; Glycoprotein; Nucleus;
KW Reference proteome.
FT CHAIN 1..310
FT /note="Tumor necrosis factor receptor type 1-associated
FT DEATH domain protein"
FT /id="PRO_0000291660"
FT DOMAIN 213..303
FT /note="Death"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00064"
FT REGION 220..287
FT /note="Interaction with KRT14 and KRT18"
FT /evidence="ECO:0000250|UniProtKB:Q15628"
FT MOTIF 147..163
FT /note="Nuclear export signal"
FT /evidence="ECO:0000269|PubMed:22561347"
FT MOTIF 229..242
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:22561347"
FT CARBOHYD 243
FT /note="(Microbial infection) N-beta-linked (GlcNAc)
FT arginine"
FT /evidence="ECO:0000269|PubMed:30902834"
FT MUTAGEN 297..299
FT /note="EDL->AAA: Dominant-negative mutant, leading to
FT enhanced ubiquitination and degradation of isoform
FT p19ARF/ARF of CDKN2A."
FT /evidence="ECO:0000269|PubMed:22561347"
SQ SEQUENCE 310 AA; 34577 MW; 225F00D4022691BB CRC64;
MAAGQNGHEE WVGSAYLFLE SAVDKVILSE AYTDPKKKVA IYKALQTALS ESGDSSDVLQ
ILKIHCSDPQ LIVQLRFCGR VLCGRFLQAY REGALRTALQ RCMAPALAQE ALRLQLELRA
GAEQLDSWLT DEERCLNYIL AQKPDRLRDE ELAELEDELC KLTCDCTGQG GAIQVASAGS
KFPVSSPTEE KPLPAACQTF LFHGQLVVNR PLTLQDQQTF ARSVGLKWRR VGRSLQRNCR
ALRDPALDSL AYEYERDGLY EQAFQLLRRF MQAEGRRATL QRLVEALEEN ELTSLAEDLL
GQAEPDGGLA
